DESCRIPTION (supplied by applicant) [unreadable] [unreadable] Brain activity requires a complex interaction between different kinds of neurons that assemble into circuits. Circuit formation and experience-dependent changes are governed by a variety of sensory inputs to form the basis for perception, memory and autoregulatory activities. In the past years a lot of information has been collected regarding the relationship between the special (anatomical) and the various physiological (sensory inputs). These studies were carried out in conjunction with elaborate electrophysiological recordings from a pair or few pairs of neurons in a particular circuit to provide information at a high temporal precision. The drawback of such approaches was the difficulty in obtaining an array of events, generated from many neurons, at high temporal precision, and hence losing crucial information related to the function of the circuit as an intact brain computing module. In recent years various optical methodologies have been developed to allow the direct observation of neuronal activity in brain circuits at high temporal and spatial precision. In this proposal the main goal is to develop new tools to allow the monitoring of specific synaptic events using optical methodologies, mainly the slow inhibitory postsynaptic potential (IPSP) which is a key determinant in controlling inhibitory signaling via G protein coupled receptors (GPCRs) (GABA-B, dopamine, opioids etc.). The GPCR-mediated signaling is relayed through G proteins to modulate the activity of G protein coupled potassium channels (GIRK/Kir3.x), which in turn, decreases the threshold for firing an action potential. The objective is to develop and employ genetically encoded GIRK channel optical reporters to allow the direct monitoring of such an activity from a specific brain region in vivo. Genetically encoded reporters will be integrated in promoter specific viral vectors and will be used to infect specific brain regions such as the barrel cortex or the olfactory bulb. Long term objective (beyond this application tenure) will be to genetically integrate these reporters in mouse (transgenic mice generation) under specific promoters to allow the constitutive expression of the reporter in specific brain neurons. This will allow the investigation of long-term sensory-dependent synaptic changes in vivo. It is important to note that this project, in addition to gaining valuable scientific information, will also allow me to get training in optical recordings of neuronal function that I can then use to train young neuroscientist in Israel upon my return. Important implication to public health will be in the form of understanding activity patterns of neuronal postsynaptic activity mediated by GPCRs and its role in drug addiction and memory. [unreadable] [unreadable] [unreadable]